Commissioned by Bayer

This NOAC dosing guide has been commissioned by Bayer, who also provided funding for its development. Bayer reviewed and approved the scope and pre-meeting documents, suggested the Chair and experts for the group, and put the dosing guide through full medical approval to ensure its compliance with appropriate regulations. The views and opinions of the contributors expressed in this document are not necessarily those of Bayer, or of Guidelines, its publisher, advisers, or advertisers.

Non-vitamin K oral anticoagulant options for patients with non‑valvular atrial fibrillation and renal impairment

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Group members

  • Professor Philip Kalra (Co-Chair, consultant nephrologist)
  • Professor Martin Cowie (Co-Chair, honorary consultant cardiologist, chair in cardiology)
  • Dr Raza Alikhan (haematologist)
  • Dr David Hargroves (consultant physician and clinical lead for stroke medicine)
  • Professor Iain MacDougall (consultant nephrologist with a specialist interest in renal anaemia and obesity in chronic kidney disease)
  • Dr Jim Moore (GPwSI heart failure)
  • Kathrine Parker (renal pharmacist)
  • Dr Albert Power (consultant nephrologist)
  • Dr Jecko Thachil (haematologist). 

Drug selection and dosing

  • NICE and European guidance recommend anticoagulant therapy to prevent stroke in patients with non-valvular atrial fibrillation (AF), including non‑vitamin K oral anticoagulants (NOACs: dabigatran etexilate, rivaroxaban, apixaban, or edoxaban) and vitamin K antagonists (warfarin):5,6–15
    • treatment choice should take into account clinical features, such as stroke and bleeding risks (using CHA2 DS2 -VASc and HAS-BLED scores), and patient preference5,6,13
    • for patients taking warfarin, optimal time in therapeutic range is associated with a lower risk of adverse events independent of underlying renal function, but patients with non-valvular AF and severe chronic kidney disease (CKD) (estimated glomerular filtration rate <30 ml/min/1.73 m2) have worse control of international normalised ratio while on warfarin16
    • the evidence suggests that NOACs are a suitable alternative to warfarin in a CKD population with CrCl 30–50 ml/min, but they are at least partly excreted via the kidneys, so healthcare professionals can find it challenging to decide on dosing taking into account factors such as age, weight, renal function, co-morbidities, concomitant drug treatment, and the relevant summary of product characteristics (SPC)5,8–12,15,17
  • Select drug treatment through shared decision‑making with the patient:
  • Use the dosing guide to aid in the choice of NOAC and determine the most appropriate dosing regimen for the selected drug:1–4
    • if creatinine clearance (CrCl) <30 ml/min, use with caution or consider seeking specialist advice
    • check for drug interactions with existing concomitant drugs and when additional medications are prescribed1–4
  • Seek specialist advice for specific populations such as patients undergoing dialysis and post-renal transplant patients

Monitoring and dosing review

  • Monitor renal function according to the latest CrCl measurement (see figure for recommendations)

Patient counselling

  • Educate the patient on how to take their NOAC and when they should contact a healthcare professional:
    • dabigatran 110 mg and 150 mg capsules should be swallowed whole with a glass of water, to facilitate delivery to the stomach1
    • rivaroxaban 15 mg and 20 mg tablets should be taken with food2
    • 2.5 mg and 5 mg apixaban tablets should be swallowed with water3
    • emphasise the importance of compliance at every opportunity
    • advise patients who have had an injury, particularly a head injury, to go to the emergency department
    • advise patients who have significant bruising or bleeding to seek urgent hospital advice
    • remind patients to always carry their anticoagulant alert card and to show it to every doctor or dentist before treatment
    • avoid co-administration of non-steroidal anti‑inflammatory drugs in patients on NOACs if possible18

Key additional considerations in the management of patients on NOACs

  • NOACs may need to be stopped before some procedures, including surgery:19,20
    • patients undergoing surgery in secondary care should be counselled on stopping and restarting drugs at their preoperative assessment
    • dental extractions can generally be performed safely in an outpatient facility by applying local haemostatic measures, without interrupting anticoagulation or by just skipping the morning dose of the NOAC5
    • it is recommended that oral anticoagulation is not interrupted for most minor surgical procedures and those procedures where bleeding is easily controllable5

Conflicts of interest

The group members have received an honorarium from Bayer to attend a meeting to develop this dosing guide. Some of the group members have also received consultancy fees from other pharmaceutical companies, which might include Bayer, for activities other than the development of this dosing guide.

References

  1. Boehringer Ingelheim Limited. Pradaxa 150 mg hard capsules—summary of product characteristicswww.medicines.org.uk/emc/product/6229 (accessed August 2018).
  2. Bayer plc. Xarelto 20 mg film-coated tablets—summary of product characteristics. www.medicines.org.uk/emc/product/2793/smpc (accessed August 2018).
  3. Bristol-Myers Squibb-Pfizer. Eliquis 5 mg film‑coated tablets—summary of product characteristicswww.medicines.org.uk/emc/product/4756/smpc (accessed August 2018).
  4. Daiichi Sankyo UK Limited. Lixiana 60 mg film-coated tablets—summary of product characteristicswww.medicines.org.uk/emc/product/6905/smpc (accessed August 2018).
  5. Steffel J, Verhamme P, Potpara T et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 2018; 39 (16): 1330–1393.
  6. Camm A, Lip G, De Caterina R et al.Eur Heart J 2012; 33 (21): 2719–2747.
  7. Department of Health. Cardiovascular disease outcomes strategy, Improving outcomes for people with or at risk of cardiovascular disease. London: DH, 2013.
  8. NICE. Dabigatran etexilate for the prevention of stroke and systemic embolism in people with atrial fibrillation. Technology Appraisal 249. NICE, 2012.
  9. NICE. Rivaroxaban for the prevention of stroke and systemic embolism in people with atrial fibrillation. Technology Appraisal 256. NICE, 2012.
  10. NICE. Apixaban for preventing stroke and systemic embolism in people with nonvalvular atrial fibrillation. Technology Appraisal 275. NICE, 2013.
  11. NICE. Edoxaban for preventing stroke and systemic embolism in people with atrial fibrillation. Technology Appraisal 355. NICE, 2015.
  12. NICE. Chronic kidney disease in adults: assessment and management. Clinical Guideline 182. NICE, 2014.
  13. NICE. Atrial fibrillation: management. Clinical Guideline 180. NICE, 2014.
  14. Boriani G, Savelieva I, Dan G et al. Europace 2015; 17 (8): 1169–1196.
  15. Turakhia M, Blankestijn P, Carrero J et al. Eur Heart J 2018; 39 (24): 2314–2325.
  16. Szummer K, Gasparini A, Eliasson S et al. J Am Heart Assoc 2017; 6 (3): e004925.
  17. Steffel J, Heidbuchel H. ‘Ten Commandments’ of the EHRA Guide for the Use of NOACs in AF. Eur Heart J 2018; 39 (16): 1322.
  18. Lutz J, Jurk K, Schinzel H. Int J Nephrol Renovasc Dis 2017; 10: 135–143.
  19. Keeling D, Tait R, Watson H. Br J Haematology 2016; 175 (4): 602–613.
  20. Scottish Dental Clinical Effectiveness Programme. Management of dental patients taking anticoagulants or antiplatelet drugs, dental clinical guidance. Dundee: SDCEP, 2015.

This dosing guide has been commissioned by Bayer, who also provided funding for its development. Bayer reviewed and approved the scope and pre-meeting documents, suggested the Chair and experts for the group, and put the dosing guide through full medical approval to ensure its compliance with appropriate regulations. The views and opinions of the contributors expressed in this document are not necessarily those of Bayer, or of Guidelines, its publisher, advisers, or advertisers.

Job code: PP-XAR-GB-0003-1

Date of preparation: December 2018